1. Field of the Invention
This invention relates to an apparatus and a method for analyzing chemical species utilizing a time-of-flight mass spectrometer. The invention further relates to improvements in the speed and sensitivity of analysis of such chemical species. Ions are formed from such species using ionization techniques such as ion-molecule reactions, thermospray, electrospray, laser ionization, and other known ionization methods. The characterization of such species is carried out through mass analysis in a time-of-flight mass spectrometer. The invention also relates to the improvement in mass resolution of ions produced from species of interest in a time-of-flight mass spectrometer. The improvement in mass resolution is brought about by the use of a supersonic ion jet in conjunction with complementary ion optics.
2. Description of the Prior Invention
Prior technology used in the analysis of the chemical species is exemplified by Cohen et al., U.S. Pat. No. 3,621,240, which describes the use of a mass spectrometer and an ion mobility detector. Quadrupole and sector mass spectrometers are widely used in chemical species analysis. These mass spectrometers suffer from several limitations. The sensitivity of the most commonly used ionization method, electron impact ionization, is limited by its ionization efficiency, which is only about 10.sup.-3 %. To obtain a complete mass spectrum, a technique is usually used where the whole mass range is scanned, sequentially admitting ions of increasing mass-to-charge ratio to an electron multiplier. This technique causes the loss of the majority of the ions produced. A complete mass spectrum typically takes greater than one second to scan, which is significantly slower than the times associated with obtaining complete mass spectra using a time-of-flight mass spectrometer.
An ion mobility detector, also known as a plasma chromatograph, has the advantage of producing an ion mobility spectrum in several tens of milliseconds. The ion mobility detector has been described in detail in the book "Plasma Chromatography" edited by T. W. Carr, Plenum Press: New York, 1984. It is operated at ambient pressure and does not require vacuum pumping. The most significant problem with the ion mobility detector is its poor resolution, which is typically 50 or less. For comparison, a typical resolution achieved using a quadrupole mass spectrometer is 300 at a mass-to-charge ratio of 300. Also, ion mobility is dependent not only on the molecular weight, but also on the size, shape, and charge density of the molecule. It is therefore very difficult to identify a compound from the spectrum alone, without comparison with an analysis conducted using a standard compound.
The problems of low sensitivity and long analysis time can be solved by using a time-of-flight mass spectrometer. The most commonly used time-of-flight mass spectrometer was described in detail in the paper by Wiley and McLaren, "Time-of-Flight Mass Spectrometer with Improved Resolution", Rev. Sci. Instrum., Vol. 26, No. 12, (1955), p. 1150. Basically, in a time-of-flight mass spectrometer, ions are produced and pulsed into a field free drift region. Assuming that all of the ions attain the same amount of energy, they will then travel in the field-free region at velocities in accordance with their mass-to-charge ratios. The mass spectrum is then a measurement of ion signals detected at different times. The advantages of a time-of-flight mass spectrometer include speed and sensitivity. A complete mass spectrum takes less than 1 millisecond to obtain. The sensitivity of a time-of-flight mass spectrometer is generally one to two orders of magnitude better than quadrupole or sector instruments.
The mass resolution of a conventional time-of-flight mass spectrometer is dependent upon the mass-to-charge ratio and is approximately 300 to 400 at a mass-to-charge ratio of 300. Much higher resolution can be obtained in a sector mass spectrometer, which can achieve a resolution of several thousand. Sector mass spectrometers are very complicated and expensive which makes them impractical for routine field analysis. The time-of-flight mass spectrometer is simpler, faster, and cheaper, but its resolution is below that of the sector instruments.
One factor contributing to the relatively poor mass resolution obtained in time-of-flight mass spectrometers (when compared to sector mass spectrometers) is the initial energy spread of the ions introduced into the field-free drift tube. In other words, ions of the same mass-to-charge ratio introduced into the flight tube at the same time and same position do not reach the detector at the same time because the initial energy of the ion influences the flight time. If all ions of the same mass and charge were to have the same initial kinetic energy and begin flight at the same time from the same position, they would reach the detector at the end of the flight tube at the same time, and infinite resolution would be achieved. Obviously, this ideal case of infinite resolution cannot be achieved because the three primary factors influencing the width of the resulting peak, or resolution, are never identical for each ion. These factors include the starting position of the ion, the time the ion flight begins, and the initial kinetic energy of each ion. Peak broadening, or a decrease in resolution, results from a combination of these three factors.
Past attempts to improve the mass resolution include ion reflection as disclosed in U.S. Pat. No. 4,072,862 to Mamyrin et al. and velocity compaction as disclosed in U.S. Pat. No. 4,458,149 to Muga et al. Both of these methods use post-acceleration add-on devices to compensate for the initial energy spread. Complicated electronics and precision machining are required to build apparatus for both of these methods.
On the other hand, the present invention uses a simple means to improve the mass resolution in a time-of-flight mass spectrometer. The ions produced in the ion source are first expanded into a supersonic jet through a small orifice which connects the ion source to the mass spectrometer vacuum chamber. A supersonic jet is a stream of molecules or ions formed as the molecules or ions flow from a higher pressure region into a region of significantly lower pressure through an opening. When the opening dimensions are much larger than the mean-free path of the molecules or ions, the molecules or ions enter the lower pressure region forming a supersonic jet. The ions or molecules in the supersonic jet have a statistical average direction or axis of flow. The supersonic expansion in the jet causes a narrowing in the energy distribution of the molecules and ions in the jet. As the ions expand through the small orifice, their internal and kinetic energies are shared through two-body collisions, and their energies become more equalized and are converted into directed mass motion. Therefore, ions forming the supersonic jet, or beam, inside the time-of-flight mass spectrometer will have very similar velocities, and subsequently the mass resolution of the instrument will be improved.
Supersonic expansions have been used to introduce neutral molecules, which are later ionized, into time-of-flight mass spectrometers using techniques described by Lubman and Jordan, "Design for Improved Resolution in a Time-of-Flight Mass Spectrometer using a Supersonic Beam and Laser Ionization Source" Rev. Sci. Instrum., Vol. 56, No. 3, (1985), p. 373, and Opsal et al., "Resolution in the Linear Time-of-Flight Mass Spectrometer", Anal. Chem., Vol. 57, No. 9, (1985), p. 1884. In both of these techniques, the neutral molecules are ionized with a UV laser beam after expansion of the supersonic jet into the mass spectrometer. The use of a laser to achieve ionization makes these techniques impractical for routine analysis. Laser ionization is an expensive method of ionization and makes the use of instruments using the technique too expensive to be used widely for routine analysis. The present invention uses an approach in which the ionization is carried out before the expansion of the sample through a small orifice or opening to form the supersonic jet. The supersonic jet then consists of both neutral molecules and ions. Engelking, "Corona Excited Supersonic Expansion", Rev. Sci.Instrum., Vol. 57, No. 9, (1986), p. 2274, has studied the energy states of ions in a supersonic jet; however, the use of supersonic ion jets has not been used to improve resolution in mass spectrometry.
Ionization of a molecular beam expanding through the small orifice can be achieved inside the mass spectrometer, not only by means of laser excitation, but also by electron impact. In electron impact ionization techniques, the distributions of internal and kinetic energies of the ions are broadened. Thus, the resolution achieved in the mass spectral analysis is lowered, because the ions entering the field-free flight tube have a spectrum of energies and their flight times are influenced by the internal and kinetic energies they possess at the times they enter the flight tube. Thus, electron impact is not practical for use in this manner in a time-of-flight mass spectrometer. Laser ionization is preferable for ionization of the molecular jet inside the mass spectrometer, but because of the complexity and expense required in laser ionization, it is impractical to use laser ionization in routine analysis with a time-of-flight mass spectrometer. Ionization at ambient pressure outside of the mass spectrometer vacuum and introduction of the ionized sample through a supersonic jet is a practical and effective method usable in routine analysis.
By placing the field-free drift tube at an angle to the axis of the directional flow of the supersonic jet beam or stream, the forward movement or energy of the ions entering the tube will not be a significant factor contributing to ion peak broadening. Pollard et al., "Electron-Impact Ionization Time-of-Flight Mass Spectrometer for Molecular Beams", Rev. Sci. Instrum., Vol. 58, No. 1, (1987), p. 32, and "Time-Resolved Mass and Energy Analysis by Position-Sensitive Time-of-Flight Detection", Rev. Sci. Instrum., Vol. 60, No. 10, (1989), p. 3171, have described the use of a flight tube perpendicular to the axis of a supersonic jet molecular beam. However, because the mass spectrometer requires ions to perform its analysis, Pollard et al. had to ionize the molecular beam once inside the mass spectrometer. Pollard et al. describe the use of an electron impact technique to ionize the molecular supersonic jet stream. By using electron impact ionization after expansion, the narrow energy distribution of the molecules in the supersonic jet is destroyed and the ions produced have very different kinetic and internal energies. This adversely affects the resolution of the mass spectrometer. Electron impact is a widely used ionization technique even though it is not a very effective ionization process. With a less effective ionization process, a larger sample must be used in order to assure that enough of the chemical species or compounds are ionized to give an acceptable response at the detector.
It is most advantageous to position the flight tube at or near a 90 degree angle to the axis of the supersonic jet stream flow. The forward movement of the ions before being directed into the flight tube has little or no effect on the rate of movement up the field-free flight tube. Thus, the resolution is not affected by the forward movement along the beam axis when the flight tube is off axis. The forward momentum may present a problem if the flight tube is narrow, because such momentum will force the molecules into the side of the flight tube. Different methods can be applied to overcome this problem. For example, a repelling field potential could be used to force the ions away from the flight tube wall.
Using a corona discharge or .sup.63 Ni Beta ion source, or other technique for the production of ions outside the reduced pressure or vacuum chamber of the mass spectrometer, a supersonic jet of ions can be obtained wherein the internal and kinetic energies of each ion fall within a relatively narrow energy band. Any sources of ion production could be used in order to produce a source of ions near the orifice through which the ions are moved in order to form the supersonic jet. Other sources include, but are not limited to, the use of laser, thermospray and electrospray ionization techniques.
The corona discharge and the .sup.63 Ni Beta ion sources are very sensitive and are very effective in the production of ions required to form the supersonic jet. Primary ions are created by these ion sources and the analyte molecules are ionized through ion-molecule reactions with primary ions. These reactions were first studied by Good et al., "Mechanism and Rate Constants of Ion-Molecule Reactions Leading to Formation of H+(H2O)n in Moist Oxygen and Air" J. Chem. Phys., Vol., 52, No. 1, (1970), p. 222. Due to the long residence time of the molecules inside the ionization chamber, a large percentage of molecules are ionized. The ionization does not cause extensive fragmentation such as that observed in electron impact ionization which is usually performed in a vacuum state. Because extensive fragmentation does not occur, the mass spectra produced, which contain parent and fragment ion signals, or peaks, are simpler, and it is easier to detect the molecules of interest.
The present invention provides for ionization of the chemical species at or near atmospheric or ambient pressure. This is advantageous because ionization and mass spectral analysis of effluents from liquid chromatographs, gas chromatographs, and supercritical fluid chromatographs can be easily achieved, because the necessary special adaptations to introduce the effluent, which is often under ambient or higher pressures, into the vacuum of the mass spectrometer are much simpler.
The ionization could actually be carried out at any pressure, but atmospheric pressure is usually the most convenient. Provided the pressure in the ionization region is significantly higher than the pressure inside the mass spectrometer apparatus, the ion jet is formed by simply making the orifice open freely between the two pressure regions. The vacuum inside the mass spectrometer draws the ionized chemical species through the orifice because of the pressure differential, and the supersonic jet is formed.
A charged surface could be used to attract or repel the ions created in the ionization region toward the orifice to create a supersonic jet with a higher concentration of ions. By providing a jet of high ion concentration, the detection limits of the analysis can be increased.
The diameter of the orifice connecting the ion production region and the vacuum chamber of the mass spectrometer is on the order of 10 microns to 500 microns. If a larger orifice is used, a larger vacuum pumping system must also be used. However, a larger orifice provides a better narrowing of the internal and kinetic energy distributions because of increased possibilities for two body collisions.
It may be desirable in some cases to introduce a gas species into the ion production region in order to increase ion production or increase ion concentration in the supersonic ion jet.